Bis(dimethyl-(2-hydroxyethyl)ammonium) 1,2-ethanediyl-bis(2-hexadecenylsuccinate)

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

3 July 1995 to 24 July 1995

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1995

Report date:

1995

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

Bis(dimethyl-(2-hydroxyethyl)ammonium) 1,2-ethanediyl-bis(2-hexadecenylsuccinate)

EC Number:

421-660-1

EC Name:

Bis(dimethyl-(2-hydroxyethyl)ammonium) 1,2-ethanediyl-bis(2-hexadecenylsuccinate)

Molecular formula:

Hill formula: C50 H96 N2 O10 CAS formula: C42 H74 O8. 2(C4 H11 N O)

IUPAC Name:

bis((2-hydroxyethyl)dimethylazanium) (4E)-3-{[2-({3-carboxylato-3-[(2E)-hexadec-2-en-2-yl]propanoyl}oxy)ethoxy]carbonyl}-4-methyloctadec-4-enoate

Constituent 2

Reference substance name:

BIS(DIMETHYL-(2-HYDROXYETHYL)AMMONIUM) 1,2-ETHANEDIYL-BIS (2-HEXADECENYLSUCCINATE)

IUPAC Name:

BIS(DIMETHYL-(2-HYDROXYETHYL)AMMONIUM) 1,2-ETHANEDIYL-BIS (2-HEXADECENYLSUCCINATE)

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: David Percival Ltd.
- Age at study initiation: 12 - 16 weeks
- Weight at study initiation: 3.01 kg
- Housing: Suspended metal cage
- Diet (e.g. ad libitum): Free access
- Water (e.g. ad libitum): Free access
- Acclimation period: 5 days minimum


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 - 24
- Humidity (%): 49 - 78
- Air changes (per hr): approximately 15
- Photoperiod (hrs dark / hrs light): 12 hours dark / 12 hours light


IN-LIFE DATES: NDA

Test system

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
- Concentration (if solution): N/A


VEHICLE
- Amount(s) applied (volume or weight with unit): N/A (no vehicle used)
- Concentration (if solution): N/A
- Lot/batch no. (if required): N/A
- Purity: N/A

Duration of treatment / exposure:

One single exposure. Eye was not washed out after exposure.

Observation period (in vivo):

21 days

Number of animals or in vitro replicates:

1

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): None
- Time after start of exposure: N/A


SCORING SYSTEM: Draize Scale for scoring ocular irritation


TOOL USED TO ASSESS SCORE: UV light / fluorescein

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #1

Time point:

other: Mean 24, 48 and 72 h

Score:

2

Max. score:

2

Reversibility:

fully reversible within: 21 days

Results 2

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

other: Mean 24, 48 and 72 h

Score:

2

Max. score:

2

Reversibility:

fully reversible within: 14 days

Results 3

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

other: Mean 24, 48 and 72 h

Score:

1.67

Max. score:

2

Reversibility:

fully reversible within: 21 days

Results 4

Irritation parameter:

iris score

Basis:

animal #1

Time point:

other: Mean 24, 48 and 72 h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 14 days

Irritant / corrosive response data:

See table below for raw data.

Reversibility of any observed effect: Changes fully reversible within 21 days

Other effects:

At the time of dose administration, an initial pain reaction was apparent for the one animal dosed. A dulling of the normal corneal lustre was observed at 1 hour following dose administration. Iris scores of 1 and conjuctival scores of 2 (redness and chemosis) were also noted at 1 hour. At that time,residual test material was also noted around the treated eye. Corneal vascularization (invading up to 3 mm of the cornea) was observed at 7 days. Within 14 days, the vascularization was noted only along the bottom edge of the cornea (approximately 5 mm in length). All ocular effects subsided within 21 days.

Any other information on results incl. tables

Rabbit Number and Sex (Bodyweight kg)	IPR = 3
	157 Female (3.01)
Time After Treatment	1 hr	24 hr	48 hr	72 hr	7 dy	14 dy	21 dy
CORNEA E = Degree of Opacity F = Area of Opacity	d   4	1*   4	2*   4	2*   4	2^v*   4	1^vv*   2	0   0
Score (E x F) x 5	0	20	40	40	40	10	0
IRIS D	1*	1*	1*	1*	1*	0	0
Score (D x 5)	5	5	5	5	5	0	0
CONJUNCTIVAE A = Redness B = Chemosis C = Discharge	2* 2* 3Re	2* 2* 2	2* 2* 2	2* 2* 2	2* 2* 2	1 0 0	0 0 0
Score (A + B + C) x 2	14	12	12	12	12	2	0
Total Score	19	37	57	57	57	12	0

Key: hr = hour(s)       dy = day(s)       IPR = initial pain reaction       d = dulling of the normal lustre of the corneal surface        Re = residual test material around treated eye       v = circumcorneal vascularisation invading up to 3mm onto the cornea

* = positive effect       vv = vascularisation along bottom ridge of cornea, approximately 5 mm in length, and invading up to 3 mm onto the cornea

Applicant's summary and conclusion

Interpretation of results:

other: risk of serious damage to eyes

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

In the one animal tested, the test material produced irritation of the cornea, iris and conjunctivae. The level of ocular responses precluded treatment of additional animals. In this study, OS 114451A should be classified as causing the risk of serious damage to eyes (R 41), taking into account the scores obtained and the persistence of effects beyond day 14.

Executive summary:

In a primary eye irritation study (525/035), 0.1mLof  neat OS 114451Awas instilled into the conjunctival sac ofthe right eye of a female New Zealand White rabbit. The eye was not washed after treatment. The animal was then observed for21days.  Irritation was scored by the method ofthe Draize scoring system.

 

In the one animal tested, the test material produced irritation of the cornea, iris and conjunctivae. The level of ocular responses precluded treatment of additional animals.  In this study,OS 114451A should be classified as causing the risk of serious damage to eyes (R 41), taking into account the scores obtained and the persistence of effects beyond day 14.